Neoadjuvant chemotherapy refers to drug treatment administered to cancer patients prior to surgery. A goal of neoadjuvant chemotherapy is to reduce the size of the cancer before surgery, thus making surgery easier and more likely to be successful. Neoadjuvant chemotherapy is used commonly in cancers that are locally advanced and/or inoperable. The use of such chemotherapy can effectively reduce the difficulty and morbidity of a subsequent surgical procedure; for example in the case of breast cancer, allowing for breast-conserving surgery to be performed instead of mastectomy.
Neoadjuvant chemotherapy has improved overall survival rates in breast cancer patients from 10-20% by local therapy alone to 30-60% with neoadjuvant chemotherapy followed by local therapy (3). However, achieving maximal benefits of neoadjuvant chemotherapy depends on the selection of an effective chemotherapy regimen. The choice of regimen by the treating oncologist is typically based on clinical and histological features and historical population response rates and not individualized to that patient. As a result, many patients are treated with unnecessary or ineffective chemotherapy, which can result in unnecessary toxicity and costs, may delay more effective treatment, and may cause the tumor to become cross-resistant to additional drugs (4).
Inadequate treatment choices for neoadjuvant therapy are partly due to the lack of accurate predictors of response in individual patients. While numerous in vitro chemosensitivity and resistance assays (CSRAs) have emerged, the assays are often limited in their utility for assessing neoadjuvant treatment, due to, for example, technical difficulties, the need for large amounts of fresh tissue (1-2 g), limited consistency in producing results (often less than 50% of submitted specimens), and the lack of reproducibility and clinical utility in predicting patient outcomes (5, 6).